But this research says no neuroplasticity occurs. Ask your competent? doctor to clarify.
ROBUST METHODS FOR QUANTIFYING NEURONAL
MORPHOLOGY AND MOLECULAR SIGNALING REVEAL THAT
PSYCHEDELICS DO NOT INDUCE NEUROPLASTICITY
March 2024
Well, hasn't your doctor already prescribed various types of psychedelics to get you recovered?
What about all these drugs for stroke recovery? Doesn't your doctor read the literature?
DMT (8 posts to November 2020)
ecstasy (19 posts to November 2012)
LSD (5 posts to September 2018)
CerAxon (5 posts to January 2012)
citicoline (15 posts to October 2011)
magic mushrooms (10 posts to October 2014)
psilocybin (14 posts to May 2014)
My 13 reasons for marijuana use post-stroke.
Don't follow me, I'm not medically trained, and I don't have a Dr. in front of my name.
The latest here:
Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review
In the mammalian brain, new neurons continue to be generated throughout life in a process known as adult neurogenesis. The role of adult-generated neurons has been broadly studied across laboratories, and mounting evidence suggests a strong link to the HPA axis and concomitant dysregulations in patients diagnosed with mood disorders. Psychedelic compounds, such as phenethylamines, tryptamines, cannabinoids, and a variety of ever-growing chemical categories, have emerged as therapeutic options for neuropsychiatric disorders, while numerous reports link their effects to increased adult neurogenesis. In this systematic review, we examine studies assessing neurogenesis or other neurogenesis-associated brain plasticity after psychedelic interventions and aim to provide a comprehensive picture of how this vast category of compounds regulates the generation of new neurons. We conducted a literature search on PubMed and Science Direct databases, considering all articles published until January 31, 2023, and selected articles containing both the words “neurogenesis” and “psychedelics”. We analyzed experimental studies using either in vivo or in vitro models, employing classical or atypical psychedelics at all ontogenetic windows, as well as human studies referring to neurogenesis-associated plasticity. Our findings were divided into five main categories of psychedelics: CB1 agonists, NMDA antagonists, harmala alkaloids, tryptamines, and entactogens. We described the outcomes of neurogenesis assessments and investigated related results on the effects of psychedelics on brain plasticity and behavior within our sample. In summary, this review presents an extensive study into how different psychedelics may affect the birth of new neurons and other brain-related processes. Such knowledge may be valuable for future research on novel therapeutic strategies for neuropsychiatric disorders.
Full text
Introduction
According to the Global Burden of Diseases study, used by the World Health Organization (WHO) for strategic planning, 264 million people, or about 4.5% of the world population, suffer from Major Depressive disorder (MDD). It is recognized as one of the most debilitating illnesses on a global scale, substantially significantly affecting daily activities, quality of life, cognitive abilities, and work productivity (James et al. 2018). MDD is characterized by persistent anhedonia, which can be continuous or episodic, and has a profound impact on self-esteem, as well as social, family, and professional life (Lépine and Briley 2011). Mood and anxiety disorders are the most prevalent mental illnesses and the third most prevalent cause of disability, contributing to the global burden of disease (WHO 2012). The majority of pharmacological interventions aiming to treat mood disorders such as MDD are benzodiazepines or selective serotonin reuptake inhibitors (SSRIs). However, these classes of drugs do not elicit positive outcomes for about 50 to 60% of patients, leading to a condition characterized as treatment-resistant depression (TRD) (Nestler et al. 2002). SSRIs, the most modern class of antidepressants, are taken daily, with an onset of the desired effects close to one month after the beginning of treatment. However, these medications can trigger adverse effects that appear early on and last for the duration of the therapy. These drugs also have a high risk of being misused, as individuals undergoing treatment tend to become physically dependent or addicted, even with the accompanying lethargy induced by them (Wong and Licinio 2001).
The pathophysiology of depression is not yet fully understood; however, empirical data from classical antidepressants have led to the widely accepted monoamine hypothesis, which predicts that this disorder arises from a deficiency or imbalance of monoamine neurotransmitters. It is worth noting that several studies support this theory. For instance, standard antidepressants primarily operate on the monoamine neurochemical route, aiming to re-establish dopamine (DA), noradrenaline (NA), and serotonin (5-HT) levels to homeostatic concentrations. The serotonin pathway is particularly important for the monoamine hypothesis, as it is the main target of many commonly used antidepressants. There are seven main classes of serotonin receptors (5-HT1 to 5-HT7), each with multiple subtypes. These receptors are involved in a wide range of physiological functions, including mood regulation, cognition, neuroplasticity, and responses to stress and anxiety (Hannon and Hoyer 2008; Savitz et al. 2009). Importantly, Psychedelics are believed to primarily activate the 5-HT2A serotonin receptors, which are G protein-coupled receptors abundant in the cerebral cortex and are responsible for the characteristic hallucinogenic effects (Geyer et al. 2009; Nichols 2016). Activation of these receptors by substances like LSD and psilocybin leads to altered sensory perception and cognition (Carhart-Harris and Nutt 2017). The 5-HT2C receptors also contribute to the effects of psychedelics by influencing mood and anxiety regulation, although to a lesser extent (Halberstadt et al. 2011). Additionally, psychedelics may act as partial agonists at 5-HT1A receptors, affecting anxiolytic and antidepressant responses, but these play a minor role compared to 5-HT2A receptors (Nichols 2016).
Moreover, monoamine antagonists like reserpine, typically used for arterial hypertension, can induce depressive symptoms when taken over extended periods (Baumeister et al. 2003; Freis 1954; De Freitas et al. 2016); Third, treatments for MDD and anxiety disorders usually require chronic, daily dosages for at least a month to produce meaningful effects (Kempermann 2002). The latter observation has also led to a reinterpretation of the long-standing monoamine hypothesis of depression to what is now termed the neurogenic hypothesis of depression. This revised theory suggests that depression correlates with a decrease in the formation of new neurons in the adult brain, a process that seems to be revived by prolonged antidepressant treatment (Jacobs et al. 2000).
Adult neurogenesis is the process by which new neurons are generated within specific brain niches throughout the life of an organism. Neurogenesis seems to be ubiquitous to all species with a central nervous system (CNS) (Barker et al. 2011), and for many of them, the process is confined to specific regions (Barnea and Pravosudov 2011; Drew et al. 2013). In rodents, it is restricted to two zones: the olfactory bulb (OB), driven by the neural stem cells (NSCs) located in the subventricular zone (SVZ), and the dentate gyrus sub-region of the hippocampus, driven by the radial glial-like cells (RGL) (Laplagne et al. 2006). The foundations of the neurogenic theory of depression are supported by empirical data from clinical and preclinical studies aimed at understanding how the neurogenesis process is reverted to homeostatic levels when SSRI chronic treatment is applied (Miller and Hen 2015). However promising, alternative pathways to the proposed hypothesis are under discussion (Data-Franco et al. 2017; N. X. Li et al. 2022; Raphael Mechoulam and Parker 2013; Sanches et al. 2021; Yuan et al. 2015) and new biochemical routes to treat depression are emerging, including the induction of neurogenesis independent of direct 5-HT modulation (Idell et al. 2017; Reiche et al. 2018). Among the chemical candidates for novel antidepressants, encouraging results have been found with the use of psychedelics (Aleksandrova and Phillips 2021; DeVos and Miller 2013; Muttoni et al. 2019).
Psychedelics are shown to induce a range of effects on brain plasticity by changing neuronal functionality at the molecular level and producing electrophysiological changes that stimulate neurotrophic signaling, including of Brain-Derived Neurotrophic Factor (BDNF), a key promoter of synaptic plasticity and neuronal survival (Browne and Lucki 2013; Castrén et al. 2007; Magaraggia et al. 2021; Muscat et al. 2021). Ultimately, neurotrophic factors induce neurite growth (Numakawa et al. 2010; Saengsawang and Rasenick 2016; Thompson et al. 2012), synaptic remodeling (Liu et al. 2013; Zhou and Song 2001), neurogenesis (García-Cabrerizo and García-Fuster 2016; Lima da Cruz et al. 2018; Liu et al. 2017), and oxidative stress reduction (Frecska et al. 2013, 2016; Szabo 2015). Thus, it is believed that psychedelics can create a window of opportunity for therapists to introduce cognitive-behavioral treatment strategies and produce long-lasting effects, which are independent of the classical pharmacological approaches to treat the hypothesized neurotransmitter imbalance (Keeler et al. 2021; Nichols 2016; Worrell and Gould 2021). Such a holistic and personalized approach can better integrate patients into the treatment process, reducing the current disconnection between popular beliefs on mental illnesses and scientific-guided psychiatric interventions (Healy 2004; Lacasse and Leo 2005).
Despite the encouraging perspectives on the applications of psychedelics, their safe employment requires a deeper understanding of their mechanisms, as the currently available compounds generally target multiple neurotransmitter systems and may lead to undesired effects (Belouin and Henningfield 2018; Brunton et al. 2011; Geyer et al. 2009). Moreover, the effects on brain physiology are shown to depend on ontogeny (Liu et al. 2006; Riga et al. 2016; Skaper and Di Marzo 2012), gender (Lee et al. 2014; Realini et al. 2011; Rubino et al. 2008), dose (Fortunato et al. 2009; Maeda et al. 2007; Marinova et al. 2017) and chemical interactions (Canales and Ferrer-Donato 2014; Zuo et al. 2018). For this reason, we sought to cover the effects of such compounds on the plasticity process associated with neurogenesis in the dentate gyrus (DG), rather than in the SVZ-OB system (Christie and Cameron 2006; Kempermann 2012). To categorize these compounds, we adapted a classification done elsewhere (Calvey and Howells 2018). Finally, we discuss findings encompassing any effect on the molecular, cellular, physiological and behavioural levels reported for in vivo or in vitro models related to neurogenesis.
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